RNA interference (RNAi) is a phenomenon in which expression of specific gene is reduced by base sequence specific destruction of mRNA triggered by small double-stranded RNA having base length of 21 to 25 (siRNA) and its application to medication is strongly expected because of its higher efficiency and base sequence specificity than an antisense nucleic acid which is in a drug trial stage. However, there are still many problems to be solved, such as transfection of siRNA to cell, assurance of safety and prolonged inhibitory effect in the cells.
Transfection of poly-(oligo)nucleotide including siRNAs into cell is difficult since they are polyanionic, which have low affinity for hydrophobic cell membrane.
Also, protection form nucleases that exist in cells to destroy exogenous nucleic acids is required to assure the safety and the prolonged inhibitory effect in the cells. Various methods are proposed so far, which are classified into the methods using a virus vector and the ones not using it.
Virus vectors are virus lack of replicative capability. The method for transferring gene into cell using the virus vector has the advantage that the processes of transfection into cell to protein synthesis may be carried out efficiently by taking the advantage of pattern of growth of virus. Recombinant virus vectors derived from adenovirus, retrovirus, lentivirus, adeno-associated virus and the like (for example, see Patent Document 1 and Non-patent Document 1). However, it has been pointed out that the method using the virus vector may cause cancer because of the virus used and some examples of death have been confirmed. Also, there is the problem of the inactivation because of the production of virus neutralizing antibody and the difficulties in the large-scale production and quality control.
On the other hand, various methods including calcium phosphate method, electroporation method, liposome method, lipofectin method, microinjection method, hydrodynamic method, the methods using complexes of carrier such as antibody and peptide and nucleic acid as the method for transfecting the nucleic acid into the target cell without using the virus vector (for example, see Non-patent Document 1).
However, conventional method for transfecting nucleic acid is yet insufficient for producing a gene medicine that introduces the nucleic acid such as siRNA in cells. In other words, novel nucleic acid carrier that has high efficiency and high reproducibility in the transfection of nucleic acids regardless of cell types, improved resistance against intracellular nuclease, sequence-specific binding and high affinity to the target nucleic acid and low cytotoxicity is needed.
A number of nucleic acid carriers and methods for transfecting nucleic acid to cell have been developed so far, and, in particular, the nucleic acid carriers and the methods for transfecting nucleic acid in cells using functional peptide such as intracellular signal peptide are attracting attention. For example, such nucleic acid carriers and methods include a method for transfecting anionic nucleic acids to cell using nuclear localization signal peptides (for example, see Patent-Documents 2 and 3), other signal peptides (for example, see Patent Document 4), and design peptide (for example, see Patent Document 5); a nucleic acid carrier having improved cell specificity using sugar-modified peptide (for example, see Patent Document 6), a functional molecule in which an amphiphilic polymer and peptide are linked (for example, see Patent Document 7), and a method in which conventional nucleic acid carrier is used with peptide (for example, see Patent Document 8).